Bcl-2 regulates the levels of the cysteine proteases ICH and CPP32/Yama in human neuronal precursor cells.
Members of the Bcl-2 family are major regulators of cell death and survival. Bcl-2 has been shown to heterodimerize with the death-inducing protein Bax, but the mechanism of action of Bcl-2 is not fully understood. Here we show, using the human NT-2 neuronal cell line, that overexpression of Bcl-2 leads to dramatic down-regulation of the cysteine proteases ICH and CPP32/Yama, which are directly involved in cell death. In addition, the nuclear enzyme poly(ADP-ribose) polymerase was cleaved in control cells but not in cells overexpressing Bcl-2 following induction of apoptosis. The mRNA levels of ICH and CPP32/Yama were differentially affected by Bcl-2 overexpression, suggesting both transcriptional and post-transcriptional effects of the protein. These results demonstrate novel mechanisms of action of Bcl-2 in influencing the expression of death effectors such as the cysteine proteases. The relative levels of Bcl-2 and of various cysteine proteases ultimately determine survival and death of different cells, including neurons.
Korhonen
L
L
Department of Developmental Neuroscience, Biomedical Center, Uppsala, Sweden.
Hamnér
S
S
Olsson
P A
PA
Lindholm
D
D
D015153:Blotting, Western; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D013234:Stem Cells
D019253:Proto-Oncogene Proteins c-bcl-2; D012313:RNA; C505407:CASP3 protein, human; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases